SP/NK-1R promotes gallbladder cancer cell proliferation and migration.

Aberrant substance P/neurokinin-1 receptor (SP/NK-1R) system activation plays a critical role in various disorders, however, little is known about the expression and the detailed molecular mechanism of the SP and NK-1R in gallbladder cancer (GBC). In this study, we firstly analyzed the expression and clinical significance of them in patients with GBC. Then, cellular assays were performed to clarify their biological role in GBC cells. Moreover, we investigated the molecular mechanisms regulated by SP/NK-1R. Meanwhile, mice xenografted with human GBC cells were analyzed regarding the effects of SP/NK1R complex in vivo. Finally, patient samples were utilized to investigate the effect of SP/NK-1R. The results showed that SP and NK-1R were highly expressed in GBC. We found that SP strongly induced GBC cell proliferation, clone formation, migration and invasion, whereas antagonizing NK-1R resulted in the opposite effects. Moreover, SP significantly enhanced the expression of NF-κB p65 and the tumor-associated cytokines, while, Akt inhibitor could reverse these effects. Further studies indicated that decreasing activation of NF-κB or Akt diminished GBC cell proliferation and migration. In consistent with results, immunohistochemical staining showed high levels of Akt, NF-κB and cytokines in tumor tissues. Most importantly, the similar conclusion was obtained in xenograft mouse model. Our findings demonstrate that NK-1R, after binding with the endogenous agonist SP, could induce GBC cell migration and spreading via modulation of Akt/NF-κB pathway.

Endoscopic retrograde cholangiopancreatography using a pediatric colonoscope in patients with Roux­en­Y gastrectomy and an intact major duodenal papilla.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y gastrectomy and an intact major duodenal papilla is challenging and difficult, with unsatisfactory outcomes using various endoscopes. Limited data are available regarding the outcomes of ERCP using a pediatric colonoscope in such patients. To evaluate the efficacy of a pediatric colonoscope in patients with Roux-en-Y gastrectomy and an major duodenal intact papilla, 93 consecutive patients with Roux-en-Y gastrectomy and an intact major duodenal papilla who underwent ERCP using a pediatric colonoscope at the Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, (Nanjing, China) between January 2018 and December 2022 were retrospectively reviewed. Following the failure of bile duct cannulation, a double-guidewire or precut technique was utilized for advanced cannulation. Interventions were performed using standard ERCP therapeutic accessories. The results indicated that distal gastrectomy with Roux-en-Y reconstruction was performed in 38 out of 93 patients, while 55 patients underwent total gastrectomy with Roux-en-Y reconstruction. The success rates associated with endoscope insertion, endoscopic cannulation and therapeutic ERCP were 88.17% (82/93), 85.37% (70/82) and 95.71% (67/70), respectively, while the clinical intervention success and complication rates were 72.04% (67/93) and 7.53% (7/93), respectively. The endoscope insertion time was 40.78±10.04 min, and the ERCP procedure time was 88.55±16.38 min. Student's t-test showed that the endoscope insertion time and the ERCP procedure time in patients undergoing distal gastrectomy were longer than those in patients undergoing total gastrectomy (P<0.05). Binary logistic regression analysis showed that age and number of previous abdominal surgeries were independent risk factors associated with endoscope insertion failure. In conclusion, the present study demonstrated that the use of a pediatric colonoscope is efficacious and safe for patients with Roux-en-Y gastrectomy and an intact major duodenal papilla undergoing ERCP.

Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects.

Quercetin is a kind of flavonoid compounds that comes from nature and is widely existed in the daily diet. Previous studies have found that quercetin has many effects such as anti-inflammatory, anti-oxidation and anti-cancer. Both in vivo and in vitro experiments have demonstrated that quercetin can exert anti-tumor effects by altering cell cycle progression, inhibiting cell proliferation, promoting apoptosis, inhibiting angiogenesis and metastasis progression, and affecting autophagy. This review summarizes the evidence for the pharmacological potential and inhibition of quercetin on cancers, supporting the viewpoint that quercetin should be adequately considered as a therapeutic agent against various cancers.

Endoscopic retrograde cholangiopancreatography in elderly patients: Difficult cannulation and adverse events.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a valuable therapeutic technique for pancreatobiliary diseases, and its application in the elderly is no longer limited. However, a higher incidence of procedure difficulty and periprocedural adverse events might be expected in elderly patients due to the presence of other medical disorders and the poor general condition of this population. AIM: To evaluate the incidence, causes, and management of difficult biliary cannulation during ERCP in elderly patients and the role of difficult cannulation as a risk factor for adverse events. METHODS: A total of 614 patients who underwent ERCP during the study period were prospectively studied and divided into two groups based on their age. One hundred and forty-six patients were aged 80 years or older and 468 patients were aged less than 80 years. The primary outcome measurements were cannulation difficulty, cannulation success rate, ERCP procedure time, and related adverse events. RESULTS: There was no difference in the incidence of difficult cannulation among the two groups (32.9% vs 34.4%, P = 0.765), as well as in the cannulation success rate (96.6% vs 96.8%, P = 0.54). The cannulation techniques were shown to be safe and efficient in achieving successful cannulation. Logistic regression analysis showed that patients aged 80 years or older were not associated with increased adverse events; however, difficult cannulation cases [adjusted odds ratio (AOR) = 3.478; 95% confidence interval (CI): 1.877-6.442; P < 0.001] and patients with Charlson Comorbidity Index ≥ 2 (AOR = 1.824; 95%CI: 0.993-3.349; P = 0.045) were more likely to develop adverse events. In contrast, other factors including age ≤ 65 (AOR = 3.460; 95%CI: 1.511-7.922; P = 0.003), female gender (AOR = 2.362; 95%CI=1.089-5.124; P = 0.030), difficult cannulation (AOR = 4.527; 95%CI: 2.078-9.860; P < 0.001), and patients with cholangitis (AOR = 3.261; 95%CI: 1.204-8.832; P = 0.020) were strongly associated with a higher rate of post-ERCP pancreatitis. CONCLUSION: Advanced age has not been proved to be a risk factor for difficult cannulation, and secondary cannulation techniques can be safely and efficaciously utilized in this group. Patients with a Charlson Comorbidity Index ≥ 2 and difficult cannulation are associated with an increased overall adverse events rate, while age ≥ 80 years is not.

Clinical Significance of Prothrombin Time in Cholangiocarcinoma Patients with Surgeries.

Background: Prothrombin time (PT) can predict survival in several types of malignancies. This study aims to investigate the predictive values of PT levels in patients with cholangiocarcinoma (CCA). Methods: We retrospectively analyzed the PT from 86 CCA patients who underwent curative resection in our hospital from December 2008 to August 2017. The relationship between PT and survival times was analyzed through univariate and multivariate analyses (Cox proportional hazards model). Kaplan-Meier curves and log-rank test were used to assess the effects of PT on overall survival (OS) and tumor recurrence-free survival (RFS). Results: Increased PT level was an effective predictor for OS (P = 0.021; hazard ratio (HR), 1.799) and RFS (P = 0.016; HR, 1.871) in CCA patients, independent of age, tumor differentiation, and TNM stage. In the low PT level group (PT < 12.3 s), patients showed a higher mean OS (23.03 m vs. 14.38 m, P = 0.0250) and RFS (17.78 m vs. 8.30 m, P = 0.0511) than those with high PT levels (PT ≥ 12.3 s). A highly significant association was observed between high PT level and shortened OS (P = 0.0373) and worse RFS (P = 0.0151). Conclusion: Preoperative increase in PT can serve as a simple but effective predictor of poor survival in CCA patients who undergo curative surgeries.

Two-year follow-up for 45 patients with achalasia who underwent peroral endoscopic myotomy.

OBJECTIVES: Achalasia is an oesophageal disorder characterized by abnormalities of peristalsis and impaired swallowing-induced relaxation. The therapeutic approach at present remains palliative. Peroral endoscopic myotomy (POEM) is thought to be less invasive and to maintain the function of the lower oesophageal sphincter postoperatively. However, the effects of POEM still need to be evaluated and understood. METHODS: We analysed the outcome for 45 achalasia patients who underwent POEM in our centre, described the details of surgery and evaluated the effects by 4 s integrated relaxation pressure (4s-IRP). All patients were followed up for at least 2 years and were assessed by the dysphagia score, the Eckardt score, oesophageal manometry and the gastro-oesophageal reflux disease (GERD) Q-questionnaire. According to the new Chicago classification of oesophageal motility using high-resolution manometry, the patients were diagnosed and classified into types I, II and III. RESULTS: The average age of the patients was 46.32 ± 19.04 years (range 26-72 years), and the ratio of women to men was 1.81. All patients were suffering from dysphagia; more than half of them experienced regurgitation. The data revealed that POEM considerably reduced the 4s-IRP, dysphagia score and Eckardt score postoperatively (all P < 0.05). The patients with type III achalasia had higher values of 4s-IRP than the others (type I, P = 0.025; type II, P = 0.022) before treatment and at 3 months after treatment (type I, P = 0.028; type II, P = 0.047). In type I patients, GERD symptoms were more likely to appear at 24 months after POEM than in type II and III patients (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: Peroral endoscopic myotomy provides definite relief of symptoms in these patients with achalasia and offers them long-term therapeutic benefit. Considering the risks of surgery, we believe that POEM is a better choice than surgery for achalasia patients and carries lower risk. However, our study is a preliminary exploration; therefore, larger-scale studies are needed for further research on POEM.

Gastrotracheal fistula: treatment with a covered self-expanding Y-shaped metallic stent.

A 67-year-old man had a sev-ere cough and pulmonary infection for 1 wk before seeking evaluation at our hospital. He had undergone esophagectomy with gastric pull-up and radiotherapy for esophageal cancer 3 years previously. After admission to our hospital, gastroscopy and bronchoscopy revealed a fistulous communication between the posterior tracheal wall near the carina and the upper residual stomach. We measured the diameter of the trachea and bronchus and determined the site and size of the fistula using multislice computed tomography and gastroscopy. A covered self-expanding Y-shaped metallic stent was implanted into the trachea and bronchus. Subsequently, the fistula was closed completely. The patient tolerated the stent well and had good palliation of his symptoms.

Endoscopic transpancreatic septotomy as a precutting technique for difficult bile duct cannulation.

AIM: To evaluate the technique of transpancreatic septotomy (TS) for cannulating inaccessible common bile ducts in endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Between May 2012 and April 2013, 1074 patients were referred to our department for ERCP. We excluded 15 patients with previous Billroth II gastrectomy, Roux-en-Y anastomosis, duodenal stenosis, or duodenal papilla tumor. Among 1059 patients who underwent ERCP, there were 163 patients with difficult bile duct cannulation. Pancreatic guidewire or pancreatic duct plastic stent assistance allowed for successful ERCP completion in 94 patients. We retrospectively analyzed clinical data from 69 failed patients (36 transpancreatic septotomies and 33 needle-knife sphincterotomies). RESULTS: Of the 69 patients who underwent precut papillotomy, common bile duct cannulation was successfully achieved in 67. The success rates in the TS and needle knife sphincterotomy (NKS) groups were 97.2% (35/36) and 96.9% (32/33), respectively, which were not significantly different (P > 0.05). Complications occurred in 11 cases, including acute pancreatitis (n = 6), bleeding (n = 2), and cholangitis (n = 3). The total frequency of complications in the TS group was lower than that in the NKS group (8.3% vs 24.2%, P < 0.05). CONCLUSION: Pancreatic guidewire or pancreatic duct plastic stent assistance improves the success rate of selective bile duct cannulation in ERCP. TS and NKS markedly improve the success rate of selective bile duct cannulation in ERCP. TS precut is safer as compared with NKS.

Endoscopic retrieval of 28 foreign bodies in a 100-year-old female after attempted suicide.

Foreign body ingestion is a common emergency situation in children with one or a few objects having been ingested. Here we report our experience using endoscopic retrieval in a female centenarian with dyspnea and foreign bodies in the esophagus. She attempted suicide by swallowing 26 coins and two other foreign bodies. A gastroscope was used to remove all foreign bodies in the lower esophagus. In total, 26 coins, one ferrous ring and one cylindrical plastic object were retrieved. To our knowledge, this is the first clinical report on retrieval of so many foreign bodies in a single case.